The purpose of this prospective controlled study was to compare healing quality following the implantation of ultraporous β-tricalcium phosphate, containing either expanded autologous mesenchymal stromal cells (trial group, 9 patients) or β-tricalcium phosphate alone (control group, 9 patients), into femoral defects during revision total hip arthroplasty. Both groups were assessed using the Harris Hip Score, radiography, and DEXA scanning at 6 weeks and 3, 6, and 12 months postoperatively. A significant difference in the bone defect healing was observed between both groups of patients (P < 0.05). In the trial group, trabecular remodeling was found in all nine patients and in the control group, in 1 patient only. Whereas, over the 12-month follow-up period, no significant difference was observed between both groups of patients in terms of the resorption of β-tricalcium phosphate, the significant differences were documented in the presence of radiolucency and bone trabeculation through the defect (P < 0.05). Using autologous mesenchymal stromal cells combined with a β-tricalcium phosphate scaffold is a feasible, safe, and effective approach for management of bone defects with compromised microenvironment. The clinical trial was registered at the EU Clinical Trials Register before patient recruitment has begun (EudraCT number 2012-005599-33).